As a traditional concept of Chinese medicine（CM）, the theory of ＂Shen（Kidney） controlling bones＂ has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development ...As a traditional concept of Chinese medicine（CM）, the theory of ＂Shen（Kidney） controlling bones＂ has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen deficiency as a pathological condition has a negative effect on the skeleton of body, specifically the disorder of bone homeostasis. Present studies indicate that Shen deficiency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal（HPA） axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis： cells that comprise bone tissue（osteo-related cells） are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.展开更多
Background Bronchial asthma （BA） and chronic obstructive pulmonary disease （COPD） are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and ...Background Bronchial asthma （BA） and chronic obstructive pulmonary disease （COPD） are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal （HPA） axis function in asthmatic rats combined with COPD. Methods Brown Norway （BN） rats were used to model These three models were compared and evaluated with the inflammatory airway diseases of BA, COPD and COPD＋BA. respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness （AHR）, inflammatory cytokines and HPA axis function. Results The inflammatory airway features and HPA axis function in rats in the COPD＋BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group （P 〈0.05）. Conclusions BN rat can be used as an animal model of COPD＋BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.展开更多
Chronic stress-induced depression is a common hallmark of many psychiatric disorders with high morbidity rate.Stress-induced dysregulation of noradrenergic system has been implicated in the pathogenesis of depression....Chronic stress-induced depression is a common hallmark of many psychiatric disorders with high morbidity rate.Stress-induced dysregulation of noradrenergic system has been implicated in the pathogenesis of depression.Lack of monoamine in the brain has been believed to be the main causative factor behind pathophysiology of major depressive disorder（MDD） and several antidepressants functions by increasing the monoamine level at the synapses in the brain.However,it is undetermined whether the noradrenergic receptor stimulation is critical for the therapeutic effect of antidepressant.Contrary to noradrenergic receptor stimulation,it has been suggested that the desensitization of β-adrenoceptor is involved in the therapeutic effect of antidepressant.In addition,enhanced noradrenaline（NA） release is central response to stress and thought to be a risk factor for the development of MDD.Moreover,fast acting antidepressant suppresses the hyperactivation of noradrenergic neurons in locus coeruleus（LC）.However,it is unclear how they alter the firing activity of LC neurons.These inconsistent reports about antidepressant effect of NA-reuptake inhibitors（NRIs） and enhanced release of NA as a stress response complicate our understanding about the pathophysiology of MDD.In this review,we will discuss the role of NA in pathophysiology of stress and the mechanism of therapeutic effect of NA in MDD.We will also discuss the possible contributions of each subtype of noradrenergic receptors on LC neurons,hypothalamic-pituitary-adrenal axis（HPA-axis） and brain derived neurotrophic factor-induced hippocampal neurogenesis during stress and therapeutic effect of NRIs in MDD.展开更多
Irritable bowel syndrome(IBS)is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role.The biopsychosocial model applied to the understanding of IBS pathophysiology...Irritable bowel syndrome(IBS)is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role.The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors,interacting with peripheral/central neuroendocrine and immune changes,may induce symptoms of IBS,modulate symptom severity,influence illness experience and quality of life,and affect outcome.The present review focuses on the role of negative affects,including depression,anxiety,and anger,on pathogenesis and clinical expression of IBS.The potential role of the autonomic nervous system,stress-hormone system,and immune system in the pathophysiology of both negative affects and IBS are taken into account.Psychiatric comorbidity and subclinical variations in levels of depression,anxiety,and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS,such as sensorimotor functions,gut microbiota,inflammation/immunity,and symptom reporting.展开更多
In recent decades, major depression has become more prevalent and research has shown that immune activation and cytokine production may be involved. This review is mainly focused on the contribution of inflammation to...In recent decades, major depression has become more prevalent and research has shown that immune activation and cytokine production may be involved. This review is mainly focused on the contribution of inflammation to depression. We first briefly introduce the inflammatory biomarkers of depression, then discuss the sources of cytokines in the brain, and finally describe the neuroimmunological mechanisms underlying the association between inflammation and depression.展开更多
In China,moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome,but its mechanisms are largely unknown.More recently,the focus has been on the wealth of information supporting stres...In China,moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome,but its mechanisms are largely unknown.More recently,the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome,and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis.In the present study,we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms.Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome.The acupoints Guanyuan（CV4） and Zusanli（ST36,bilateral） were simultaneously administered moxibustion.Untreated chronic fatigue syndrome rats and normal rats were used as controls.Results from the forced swimming test,open field test,tail suspension test,real-time PCR,enzyme-linked immunosorbent assay,and western blot assay showed that moxibustion treatment decreased m RNA expression of corticotropin-releasing hormone in the hypothalamus,and adrenocorticotropic hormone and corticosterone levels in plasma,and markedly increased progranulin m RNA and protein expression in the hippocampus.These findings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome,at least in part,by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.展开更多
Sini Powder(SP), a traditional Chinese herbal formula, has long been used to treat depression in patients, although the underlying mechanisms remain to be elucidated. In the present study, we found that rats treated w...Sini Powder(SP), a traditional Chinese herbal formula, has long been used to treat depression in patients, although the underlying mechanisms remain to be elucidated. In the present study, we found that rats treated with SP extract for 7 days showed a significant increase in swimming time and reduction in immobility time in forced swimming test in a dose-dependent manner, without changes in locomotion. These effects could be attributed to SP's modulation of the hypothalamus-pituitary-adrenal axis, because a single pretreatment of SP extract could rescue increased serum corticosterone and plasma adrenocorticotropin levels induced by acute elevated platform stress. A single pretreatment of SP extract could also elevate the m RNA expression of hippocampal glucocorticoid receptors. In conclusion, our results suggest that SP extract may act as an anti-stress medication to produce antidepressant-like effects.展开更多
BACKGROUND： The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE...BACKGROUND： The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE： To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor （MR） and glucocorticoid receptor （GR） in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS： Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone （CRH） and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS： A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups （n = 45）. Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES： Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS： Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed （P 〈 0.05-0.01）. CONCLUSION： Negative feedback from the hippocamp展开更多
The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an impo...The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity.The glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic mechanisms.Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive functions.An appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive impairment.Patients with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression.This review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive activities.It emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive impairment.This provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.展开更多
基金Supported by the Major Science and Technology Special Project of Zhejiang Province to TONG Pei-jian(No.2014C03035)the Zhejiang Provincial Major Science and Technology Project of Medical and Health of China to TONG Pei-jian(No.201487674)Cultivation Program for Innovative Talent Graduate Students to XU Tao-tao(No.311100G00901)from Zhejiang Chinese Medical University
文摘As a traditional concept of Chinese medicine（CM）, the theory of ＂Shen（Kidney） controlling bones＂ has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen deficiency as a pathological condition has a negative effect on the skeleton of body, specifically the disorder of bone homeostasis. Present studies indicate that Shen deficiency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal（HPA） axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis： cells that comprise bone tissue（osteo-related cells） are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.
文摘Background Bronchial asthma （BA） and chronic obstructive pulmonary disease （COPD） are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal （HPA） axis function in asthmatic rats combined with COPD. Methods Brown Norway （BN） rats were used to model These three models were compared and evaluated with the inflammatory airway diseases of BA, COPD and COPD＋BA. respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness （AHR）, inflammatory cytokines and HPA axis function. Results The inflammatory airway features and HPA axis function in rats in the COPD＋BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group （P 〈0.05）. Conclusions BN rat can be used as an animal model of COPD＋BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.
文摘Chronic stress-induced depression is a common hallmark of many psychiatric disorders with high morbidity rate.Stress-induced dysregulation of noradrenergic system has been implicated in the pathogenesis of depression.Lack of monoamine in the brain has been believed to be the main causative factor behind pathophysiology of major depressive disorder（MDD） and several antidepressants functions by increasing the monoamine level at the synapses in the brain.However,it is undetermined whether the noradrenergic receptor stimulation is critical for the therapeutic effect of antidepressant.Contrary to noradrenergic receptor stimulation,it has been suggested that the desensitization of β-adrenoceptor is involved in the therapeutic effect of antidepressant.In addition,enhanced noradrenaline（NA） release is central response to stress and thought to be a risk factor for the development of MDD.Moreover,fast acting antidepressant suppresses the hyperactivation of noradrenergic neurons in locus coeruleus（LC）.However,it is unclear how they alter the firing activity of LC neurons.These inconsistent reports about antidepressant effect of NA-reuptake inhibitors（NRIs） and enhanced release of NA as a stress response complicate our understanding about the pathophysiology of MDD.In this review,we will discuss the role of NA in pathophysiology of stress and the mechanism of therapeutic effect of NA in MDD.We will also discuss the possible contributions of each subtype of noradrenergic receptors on LC neurons,hypothalamic-pituitary-adrenal axis（HPA-axis） and brain derived neurotrophic factor-induced hippocampal neurogenesis during stress and therapeutic effect of NRIs in MDD.
文摘Irritable bowel syndrome(IBS)is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role.The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors,interacting with peripheral/central neuroendocrine and immune changes,may induce symptoms of IBS,modulate symptom severity,influence illness experience and quality of life,and affect outcome.The present review focuses on the role of negative affects,including depression,anxiety,and anger,on pathogenesis and clinical expression of IBS.The potential role of the autonomic nervous system,stress-hormone system,and immune system in the pathophysiology of both negative affects and IBS are taken into account.Psychiatric comorbidity and subclinical variations in levels of depression,anxiety,and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS,such as sensorimotor functions,gut microbiota,inflammation/immunity,and symptom reporting.
基金supported by the National Natural Science Foundation of China (81071103 and 81271500)
文摘In recent decades, major depression has become more prevalent and research has shown that immune activation and cytokine production may be involved. This review is mainly focused on the contribution of inflammation to depression. We first briefly introduce the inflammatory biomarkers of depression, then discuss the sources of cytokines in the brain, and finally describe the neuroimmunological mechanisms underlying the association between inflammation and depression.
基金funded by the National Natural Science Foundation (No.81303034 and 81303031)China Postdoctoral Science Foundation (No.KLF501004)Development Project of Shanghai Peak Disciplines-Integrated Chinese and Western Medicine
文摘In China,moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome,but its mechanisms are largely unknown.More recently,the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome,and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis.In the present study,we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms.Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome.The acupoints Guanyuan（CV4） and Zusanli（ST36,bilateral） were simultaneously administered moxibustion.Untreated chronic fatigue syndrome rats and normal rats were used as controls.Results from the forced swimming test,open field test,tail suspension test,real-time PCR,enzyme-linked immunosorbent assay,and western blot assay showed that moxibustion treatment decreased m RNA expression of corticotropin-releasing hormone in the hypothalamus,and adrenocorticotropic hormone and corticosterone levels in plasma,and markedly increased progranulin m RNA and protein expression in the hippocampus.These findings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome,at least in part,by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.
基金supported by the National Basic Research Program funded by Ministry of Science and Technology of People’s Republic of China(No.2011CB505100)
文摘Sini Powder(SP), a traditional Chinese herbal formula, has long been used to treat depression in patients, although the underlying mechanisms remain to be elucidated. In the present study, we found that rats treated with SP extract for 7 days showed a significant increase in swimming time and reduction in immobility time in forced swimming test in a dose-dependent manner, without changes in locomotion. These effects could be attributed to SP's modulation of the hypothalamus-pituitary-adrenal axis, because a single pretreatment of SP extract could rescue increased serum corticosterone and plasma adrenocorticotropin levels induced by acute elevated platform stress. A single pretreatment of SP extract could also elevate the m RNA expression of hippocampal glucocorticoid receptors. In conclusion, our results suggest that SP extract may act as an anti-stress medication to produce antidepressant-like effects.
基金the Postdoctoral Science Foundation of China,No. 20060390301the National Natural Science Foundation of China,No.30600341the Ph.D.Program Foundation of Ministry of Education of China,No.20050159011
文摘BACKGROUND： The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE： To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor （MR） and glucocorticoid receptor （GR） in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS： Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone （CRH） and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS： A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups （n = 45）. Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES： Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS： Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed （P 〈 0.05-0.01）. CONCLUSION： Negative feedback from the hippocamp
基金supported by the National Natural Science Foundation of China,No.82371444(to YZ)the Natural Science Foundation of Hubei Province,No.2022CFB216(to XC)the Key Research Project of Ministry of Science and Technology of China,No.2022ZD021160(to YZ)。
文摘The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity.The glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic mechanisms.Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive functions.An appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive impairment.Patients with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression.This review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive activities.It emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive impairment.This provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.
